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What Causes Lactic Acidosis In Diabetics?

Metformin And Fatal Lactic Acidosis

Metformin And Fatal Lactic Acidosis

Publications Published: July 1998 Information on this subject has been updated. Read the most recent information. Dr P Pillans,former Medical Assessor, Centre for Adverse Reactions Monitoring (CARM), Dunedin Metformin is a useful anti-hyperglycaemic agent but significant mortality is associated with drug-induced lactic acidosis. Significant renal and hepatic disease, alcoholism and conditions associated with hypoxia (eg. cardiac and pulmonary disease, surgery) are contraindications to the use of metformin. Other risk factors for metformin-induced lactic acidosis are sepsis, dehydration, high dosages and increasing age. Metformin remains a major reported cause of drug-associated mortality in New Zealand. Of the 12 cases of lactic acidosis associated with metformin reported to CARM since 1977, 2 occurred in the last year and 8 cases had a fatal outcome. Metformin useful but small risk of potentially fatal lactic acidosis Metformin is a useful therapeutic agent for obese non-insulin dependent diabetics and those whose glycaemia cannot be controlled by sulphonylurea monotherapy. Lactic acidosis is an uncommon but potentially fatal adverse effect. The reported frequency of lactic acidosis is 0.06 per 1000 patient-years, mostly in patients with predisposing factors.1 Examples of metformin-induced lactic acidosis cases reported to CARM include: A 69-year-old man, with renal and cardiac disease, was prescribed metformin due to failing glycaemic control on glibenclamide monotherapy. He was well for six weeks, then developed lactic acidosis and died within 3 days. Post-surgical lactic acidosis caused the death of a 70-year-old man whose metformin was not withdrawn at the time of surgery. A 56-year-old woman, with no predisposing disease, died from lactic acidosis following major Continue reading >>

Review Metformin-associated Lactic Acidosis: Current Perspectives On Causes And Risk

Review Metformin-associated Lactic Acidosis: Current Perspectives On Causes And Risk

Abstract Although metformin has become a drug of choice for the treatment of type 2 diabetes mellitus, some patients may not receive it owing to the risk of lactic acidosis. Metformin, along with other drugs in the biguanide class, increases plasma lactate levels in a plasma concentration-dependent manner by inhibiting mitochondrial respiration predominantly in the liver. Elevated plasma metformin concentrations (as occur in individuals with renal impairment) and a secondary event or condition that further disrupts lactate production or clearance (e.g., cirrhosis, sepsis, or hypoperfusion), are typically necessary to cause metformin-associated lactic acidosis (MALA). As these secondary events may be unpredictable and the mortality rate for MALA approaches 50%, metformin has been contraindicated in moderate and severe renal impairment since its FDA approval in patients with normal renal function or mild renal insufficiency to minimize the potential for toxic metformin levels and MALA. However, the reported incidence of lactic acidosis in clinical practice has proved to be very low (< 10 cases per 100,000 patient-years). Several groups have suggested that current renal function cutoffs for metformin are too conservative, thus depriving a substantial number of type 2 diabetes patients from the potential benefit of metformin therapy. On the other hand, the success of metformin as the first-line diabetes therapy may be a direct consequence of conservative labeling, the absence of which could have led to excess patient risk and eventual withdrawal from the market, as happened with earlier biguanide therapies. An investigational delayed-release metformin currently under development could potentially provide a treatment option for patients with renal impairment pending the resu Continue reading >>

Biochemistry - Why Would Lactate Be High In Diabetics? - Biology Stack Exchange

Biochemistry - Why Would Lactate Be High In Diabetics? - Biology Stack Exchange

Why are lactate level high in diabetes? For example, type II diabetes are resistant to insulin. If those patients are insulin resistant their gluconeogenesis should be working at a high rate and, because of that, lactate uptake by the liver should be removing lactate from the blood. Alternatively, type I diabetics don't produce insulin, so the ratio insulin/glucagon would always be very low and gluconeogenesis should be stimulated... So I don't understand why lactate levels are high in diabetes... Can someone help me? Can you provide any references in support of your assertion that diabetes is associated with elevated levels of lactate? Alan Boyd Jan 7 '14 at 19:43 It was just an experiment that we did in school, with diabetic rats and normal rats. Diabetic rats had higher levels of lactate and my professor said that it is because the diabetic rats don't do gluconeogenesis and so, lactate accumulates in the plasma... But it doesn't make sense for me! user5354 Jan 7 '14 at 19:46 This condition is also known as "lactic acidosis" and can be pretty dangerous, since it influences the pH of the blood. When we metabolize glucose to produce ATP and NADH it is metabolized finally to pyruvate in a process called glyolysis (I am not going into detail here since this is nicely explained in the Wikipedia). Pyruvate can then be used further in the body in the Gluconeogenesis , the Citric acid cycle and other pathways. If a lot of energy is needed Pyruvate is converted by the pyruvate dehydrogenase into acetyl-CoA. The problem with diabetes is that the pyruvate dehydrogenase can be inhibited in diabetes. If the body then needs a lot of energy pyruvate will be converted into lactate which is released by the cells into the bloodstream.Gluconeogenesis cannot be activated since this need Continue reading >>

Lactic Acidosis As A Cause Of Nonketotic Acidosis In Diabetic Patients

Lactic Acidosis As A Cause Of Nonketotic Acidosis In Diabetic Patients

This article has no abstract; the first 100 words appear below. SEVERE metabolic acidosis, when it occurs in diabetic patients, is generally the result of excessive hepatic production of acetoacetic and beta-hydroxybutyric acid. Exceptional cases of metabolic acidosis in diabetic patients whose urine has failed to give a positive reaction for acetoacetic acid have long been recognized.1 In certain cases increased concentrations of beta-oxybutyric acids have been demonstrated in the plasma. A failure of renal excretion of acetoacetic acid, usually attributed to shock, has been proposed as an explanation of these cases.2 , 3 In other cases examinations of the plasma or tissues for beta-oxybutyric acids by qualitative or quantitative procedures have failed . . . *From the Metabolism Division, Department of Internal Medicine, Washington University School of Medicine. We are indebted to Drs. Thomas J. Walsh, William D. Perry and Harold Roberts for permission to study and report these cases. Continue reading >>

Lactic Acidosis: Symptoms, Causes, And Treatment

Lactic Acidosis: Symptoms, Causes, And Treatment

Lactic acidosis occurs when the body produces too much lactic acid and cannot metabolize it quickly enough. The condition can be a medical emergency. The onset of lactic acidosis might be rapid and occur within minutes or hours, or gradual, happening over a period of days. The best way to treat lactic acidosis is to find out what has caused it. Untreated lactic acidosis can result in severe and life-threatening complications. In some instances, these can escalate rapidly. It is not necessarily a medical emergency when caused by over-exercising. The prognosis for lactic acidosis will depend on its underlying cause. A blood test is used to diagnose the condition. Lactic acidosis symptoms that may indicate a medical emergency include a rapid heart rate and disorientaiton. Typically, symptoms of lactic acidosis do not stand out as distinct on their own but can be indicative of a variety of health issues. However, some symptoms known to occur in lactic acidosis indicate a medical emergency. Lactic acidosis can occur in people whose kidneys are unable to get rid of excess acid. Even when not related to just a kidney condition, some people's bodies make too much lactic acid and are unable to balance it out. Diabetes increases the risk of developing lactic acidosis. Lactic acidosis may develop in people with type 1 and 2 diabetes mellitus , especially if their diabetes is not well controlled. There have been reports of lactic acidosis in people who take metformin, which is a standard non-insulin medication for treating type 2 diabetes mellitus. However, the incidence is low, with equal to or less than 10 cases per 100,000 patient-years of using the drug, according to a 2014 report in the journal Metabolism. The incidence of lactic acidosis is higher in people with diabetes who Continue reading >>

Lactic Acidosis In A Patient With Type 2 Diabetes Mellitus

Lactic Acidosis In A Patient With Type 2 Diabetes Mellitus

Go to: Introduction A 49-year-old man presented to the emergency department complaining of dyspnea for 2 days. He had a history of hypertension, type 2 diabetes mellitus, atrial fibrillation, and a severe dilated cardiomyopathy. He had been hospitalized several times in the previous year for decompensated congestive heart failure (most recently, 1 month earlier). The plasma creatinine concentration was 1.13 mg/dl on discharge. Outpatient medications included insulin, digoxin, warfarin, spironolactone, metoprolol succinate, furosemide (80 mg two times per day; increased from 40 mg daily 1 month earlier), metolazone (2.5 mg daily; added 1 month earlier), and metformin (2500 mg in three divided doses; increased from 1000 mg 1 month earlier). Physical examination revealed an obese man in moderate respiratory distress. The temperature was 36.8°C, BP was 119/83 mmHg, and heart rate was 96 per minute. Peripheral hemoglobin oxygen saturation was 97% on room air, with a respiratory rate of 26 per minute. The heart rhythm was irregularly irregular; there was no S3 or murmur. Jugular venous pressure was about 8 cm. There was 1+ edema at the ankles. A chest radiograph showed cardiomegaly and central venous prominence. The N-terminal pro-B-type natriuretic peptide level was 5137 pg/ml (reference range = 1–138 pg/ml). The peripheral hemoglobin concentration was 12.5 g/dl, the white blood cell count was 12,500/µl (76% granulocytes), and the platelet count was 332,000/µL. Initial plasma chemistries are shown in Table 1. The impression was decompensated congestive heart failure. After administration of furosemide (160 mg intravenously), the urine output increased to 320 ml over the next 1 hour. There was no improvement in the dyspnea. Within 2 hours, the patient’s BP fell to 100/ Continue reading >>

What Is Lactic Acidosis?: Signs, Symptoms, Causes And Treatment

What Is Lactic Acidosis?: Signs, Symptoms, Causes And Treatment

What is lactic acidosis? It is a condition where lactate builds up in the body which leads to extremely low pH levels in the blood. Normally, your blood is alkaline or slightly basic. Lactic acidosis occurs when your blood is much more acidic than usual. Changes in blood pH levels can adversely affect your body’s organs. Lactic acidosis is a form of metabolic acidosis characterized by excessive accumulation of acid as a result of the body failing to metabolize lactic acidosis. Metabolic acidosis is a medical state that occurs when there is reduced systemic pH because of a decrease in bicarbonate or an increase in hydrogen ion concentration. Accumulation of lactic acids happens when there is inadequate oxygen in the muscles that is required to break down the glycogen and glucose for energy. In a normal body, lactate will exit muscle cells and travel to the liver, where it will be oxidized to pyruvate, and later converted to glucose. Glucose refers to a form of sugar which is one of the main sources of energy for the body. When there is reduced oxygen in the tissue, there will be a build up of lactic acid. This medical condition usually starts in the kidneys. Lactic acidosis normally occurs when the kidneys fail to excrete excess acids from the body. As a result, lactic acid accumulates in the body faster than it is removed. This build up of lactic acid leads to a pH imbalance in the body. There are two forms of lactic acid, that is D-lactate and L-lactate. D-lactate is a form produced in bacterial metabolism and may build up in patients who have had a gastric bypass or have short gut syndrome. On the other hand, L-lactic is produced from human metabolism. Both L-lactic and D-lactic are produced from pyruvate and metabolized to pyruvate by an enzyme known as lactate deh Continue reading >>

What Is Lactic Acidosis In Type 2 Diabetes? [causes & Solutions]

What Is Lactic Acidosis In Type 2 Diabetes? [causes & Solutions]

Lactic acidosis is when lactic acid builds ups in the bloodstream faster than it can be removed. Lactic acid is produced when oxygen levels in the body drop. The most common cause of lactic acidosis is intense exercise, usually in the form of lifting weights. When you get a “pump” or “burn” in the muscle, that’s from lactic acid build-up. The Cause In Diabetics But lactic acidosis usually happens in type 2 diabetes due to a glucose-lowering medication called, Metformin (Glucophage). The risk of lactic acidosis also goes up if you: have heart failure or a lung ailment have kidney or liver problems drink alcohol Also, dehydration can affect your kidney or liver function and increase your risk of lactic acidosis, especially when taking Metformin. So, make sure you’re always hydrated with clean water. The Symptoms Typical symptoms of lactic acidosis in diabetics is: diarrhea fast and shallow breathing muscle pain or cramping weakness tiredness or unusual sleepiness If you’re feeling nausea or weakness, you should contact your doctor and do a blood test to check electrolyte levels and see if you do have lactic acidosis. The Solutions FIRST – You need to make sure you’re always hydrated. That means to drink plenty of purified water and avoid alcohol and caffeinated beverages – since both cause dehydration. SECOND – You should consider getting OFF the drug Metformin if you’re using it, which is the primary cause of the lactic acidosis. Speak to your doctor about alternatives, preferably something natural. THIRD – It’s best to control your blood sugar and glucose levels naturally – through simple life-style changes … because this is the best long-term solution without worry of negative side-effects from drugs, such as lactic acidosis or kidney an Continue reading >>

Causes Of Lactic Acidosis

Causes Of Lactic Acidosis

INTRODUCTION AND DEFINITION Lactate levels greater than 2 mmol/L represent hyperlactatemia, whereas lactic acidosis is generally defined as a serum lactate concentration above 4 mmol/L. Lactic acidosis is the most common cause of metabolic acidosis in hospitalized patients. Although the acidosis is usually associated with an elevated anion gap, moderately increased lactate levels can be observed with a normal anion gap (especially if hypoalbuminemia exists and the anion gap is not appropriately corrected). When lactic acidosis exists as an isolated acid-base disturbance, the arterial pH is reduced. However, other coexisting disorders can raise the pH into the normal range or even generate an elevated pH. (See "Approach to the adult with metabolic acidosis", section on 'Assessment of the serum anion gap' and "Simple and mixed acid-base disorders".) Lactic acidosis occurs when lactic acid production exceeds lactic acid clearance. The increase in lactate production is usually caused by impaired tissue oxygenation, either from decreased oxygen delivery or a defect in mitochondrial oxygen utilization. (See "Approach to the adult with metabolic acidosis".) The pathophysiology and causes of lactic acidosis will be reviewed here. The possible role of bicarbonate therapy in such patients is discussed separately. (See "Bicarbonate therapy in lactic acidosis".) PATHOPHYSIOLOGY A review of the biochemistry of lactate generation and metabolism is important in understanding the pathogenesis of lactic acidosis [1]. Both overproduction and reduced metabolism of lactate appear to be operative in most patients. Cellular lactate generation is influenced by the "redox state" of the cell. The redox state in the cellular cytoplasm is reflected by the ratio of oxidized and reduced nicotine ad Continue reading >>

What Is A Lactic Acid Blood Test?

What Is A Lactic Acid Blood Test?

It’s a test that measures the amount of lactic acid (also called “lactate”) in your blood. This acid is made in muscle cells and red blood cells. It forms when your body turns food into energy. Your body relies on this energy when its oxygen levels are low. Oxygen levels might drop during an intense workout or when you have an infection or disease. Once you finish your workout or recover from the illness, your lactic acid level tends to go back to normal. But sometimes, it doesn't. Higher-than-normal lactic acid levels can lead to a condition called lactic acidosis. If it’s severe enough, it can upset your body’s pH balance, which indicates the level of acid in your blood. Lactic acidosis can lead to these symptoms: It’s a simple blood test. Your doctor will draw blood from a vein or artery using a needle. In rare cases, he may take a sample of cerebrospinal fluid from your spinal column during a procedure called a spinal tap. Normally, you don’t have to adjust your routine to prepare for the test. If your lactic acid level is normal, you don’t have lactic acidosis. Your cells are making enough oxygen. It also tells your doctor that something other than lactic acidosis is causing your symptoms. He’ll likely order other tests to find out what it is. If your lactic acid level is high, it could be caused by a number of things. Most often, it’s because you have a condition that makes it hard for you to breathe in enough oxygen. Some of these conditions could include: Severe lung disease or respiratory failure Fluid build-up in your lungs Very low red blood cell count (severe anemia) A higher-than-normal lactic acid level in your blood can also be a sign of problems with your metabolism. And, your body might need more oxygen than normal because you have o Continue reading >>

Glyburide And Metformin (oral Route)

Glyburide And Metformin (oral Route)

Precautions Drug information provided by: Micromedex It is very important that your doctor check your progress at regular visits to make sure this medicine is working properly. Blood tests may be needed to check for unwanted effects. Under certain conditions, too much metformin can cause lactic acidosis. The symptoms of lactic acidosis are severe and quick to appear. They usually occur when other health problems not related to the medicine are present and very severe, such as a heart attack or kidney failure. The symptoms of lactic acidosis include abdominal or stomach discomfort; decreased appetite; diarrhea; fast, shallow breathing; a general feeling of discomfort; muscle pain or cramping; and unusual sleepiness, tiredness, or weakness. If you have any symptoms of lactic acidosis, get emergency medical help right away. It is very important to carefully follow any instructions from your health care team about: Alcohol—Drinking alcohol may cause severe low blood sugar. Discuss this with your health care team. Other medicines—Do not take other medicines unless they have been discussed with your doctor. This especially includes nonprescription medicines such as aspirin, and medicines for appetite control, asthma, colds, cough, hay fever, or sinus problems. Counseling—Other family members need to learn how to prevent side effects or help with side effects if they occur. Also, patients with diabetes may need special counseling about diabetes medicine dosing changes that might occur because of lifestyle changes, such as changes in exercise and diet. Furthermore, counseling on contraception and pregnancy may be needed because of the problems that can occur in patients with diabetes during pregnancy. Travel—Keep your recent prescription and your medical history with yo Continue reading >>

Hyperglycaemic Crises And Lactic Acidosis In Diabetes Mellitus

Hyperglycaemic Crises And Lactic Acidosis In Diabetes Mellitus

Hyperglycaemic crises are discussed together followed by a separate section on lactic acidosis. DIABETIC KETOACIDOSIS (DKA) AND HYPERGLYCAEMIC HYPEROSMOLAR STATE (HHS) Definitions DKA has no universally agreed definition. Alberti proposed the working definition of “severe uncontrolled diabetes requiring emergency treatment with insulin and intravenous fluids and with a blood ketone body concentration of >5 mmol/l”.1 Given the limited availability of blood ketone body assays, a more pragmatic definition comprising a metabolic acidosis (pH <7.3), plasma bicarbonate <15 mmol/l, plasma glucose >13.9 mmol/l, and urine ketostix reaction ++ or plasma ketostix ⩾ + may be more workable in clinical practice.2 Classifying the severity of diabetic ketoacidosis is desirable, since it may assist in determining the management and monitoring of the patient. Such a classification is based on the severity of acidosis (table 1). A caveat to this approach is that the presence of an intercurrent illness, that may not necessarily affect the level of acidosis, may markedly affect outcome: a recent study showed that the two most important factors predicting mortality in DKA were severe intercurrent illness and pH <7.0.3 HHS replaces the older terms, “hyperglycaemic hyperosmolar non-ketotic coma” and “hyperglycaemic hyperosmolar non-ketotic state”, because alterations of sensoria may be present without coma, and mild to moderate ketosis is commonly present in this state.4,5 Definitions vary according to the degree of hyperglycaemia and elevation of osmolality required. Table 1 summarises the definition of Kitabchi et al.5 Epidemiology The annual incidence of DKA among subjects with type 1 diabetes is between 1% and 5% in European and American series6–10 and this incidence appear Continue reading >>

Diabetes And Metformin Faqs

Diabetes And Metformin Faqs

Tweet Although one of the most common drugs for type 2 diabetics, Metformin can still confuse diabetic patients. This set of FAQs are intended for information purposes, and should not replace or supersede the advice of a doctor or qualified medical professional. If you have a question about diabetes and Metformin that is not covered here, please ask the community in the Diabetes forum. Should all type 2 diabetics take Meformin? One side effect of taking Metformin is lactic acidosis, and for this reason some diabetics should not take Metformin unless specifically advised to do so by their GP or diabetes healthcare team. For this reason, diabetics with kidney problems, liver problems, and heart problems are often advised to avoid Metformin. Similarly, diabetics that are dehydrated, drink alcohol a lot, or are going to have an x-ray or surgery. For some pregnant diabetics, Metformin may not be the best choice, but in all instances this should be discussed with your doctor. Can young diabetics take Metformin? Metformin has been proven in clinical trials to lower glucose levels amongst children between 10-16 years of age suffering from type 2 diabetes. Research is less conclusive about children under 10 and children taking Metformin alongside other treatments, but your diabetes health care team should be able to elaborate on this. How much Metformin should I take? This will depend entirely on your condition, and your doctor will be able to tell you how much Metformin to take, when you should take it, and how you should take it. Usually, diabetics start out on a low dose of Metformin, and this is slowly increased until blood sugar responds. Doctors often put diabetics on combination courses with other medication, including insulin. If I take Metformin, can I stop my diet and Continue reading >>

Lactic Acidosis In A Patient With Type 2 Diabetes Mellitus

Lactic Acidosis In A Patient With Type 2 Diabetes Mellitus

Introduction A 49-year-old man presented to the emergency department complaining of dyspnea for 2 days. He had a history of hypertension, type 2 diabetes mellitus, atrial fibrillation, and a severe dilated cardiomyopathy. He had been hospitalized several times in the previous year for decompensated congestive heart failure (most recently, 1 month earlier). The plasma creatinine concentration was 1.13 mg/dl on discharge. Outpatient medications included insulin, digoxin, warfarin, spironolactone, metoprolol succinate, furosemide (80 mg two times per day; increased from 40 mg daily 1 month earlier), metolazone (2.5 mg daily; added 1 month earlier), and metformin (2500 mg in three divided doses; increased from 1000 mg 1 month earlier). Physical examination revealed an obese man in moderate respiratory distress. The temperature was 36.8°C, BP was 119/83 mmHg, and heart rate was 96 per minute. Peripheral hemoglobin oxygen saturation was 97% on room air, with a respiratory rate of 26 per minute. The heart rhythm was irregularly irregular; there was no S3 or murmur. Jugular venous pressure was about 8 cm. There was 1+ edema at the ankles. A chest radiograph showed cardiomegaly and central venous prominence. The N-terminal pro-B-type natriuretic peptide level was 5137 pg/ml (reference range = 1–138 pg/ml). The peripheral hemoglobin concentration was 12.5 g/dl, the white blood cell count was 12,500/µl (76% granulocytes), and the platelet count was 332,000/µL. Initial plasma chemistries are shown in Table 1. The impression was decompensated congestive heart failure. After administration of furosemide (160 mg intravenously), the urine output increased to 320 ml over the next 1 hour. There was no improvement in the dyspnea. Within 2 hours, the patient’s BP fell to 100/64 mmHg Continue reading >>

A Side Effect You Should Know About

A Side Effect You Should Know About

The glucose-lowering medication metformin (Glucophage) could cause lactic acidosis if your kidneys and liver are not working efficiently. Lactic acidosis is when high levels build up in the blood of a substance called lactic acid — a chemical that is normally produced by your body in small amounts and removed by your liver and kidneys. The risk of lactic acidosis goes up if you: have heart failure or a lung ailment have kidney or liver problems drink alcohol heavily In these cases, you might not be able to take metformin. If you don't have one of these problems, you are at a very low risk for developing lactic acidosis from metformin. You should, however, contact your doctor immediately if you suddenly develop any of these symptoms of lactic acidosis: diarrhea fast and shallow breathing muscle pain or cramping weakness tiredness or unusual sleepiness You should also let your doctor know if you get the flu or any illness that results in severe vomiting, diarrhea, and/or fever, or if your intake of fluids becomes significantly reduced. Severe dehydration can affect your kidney or liver function and increase your risk of lactic acidosis from metformin. Continue reading >>

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